Notch2: a second mammalian Notch gene

Development ◽  
1992 ◽  
Vol 116 (4) ◽  
pp. 931-941 ◽  
Author(s):  
G. Weinmaster ◽  
V.J. Roberts ◽  
G. Lemke
Keyword(s):  
Cell Fate ◽  
Expression Patterns ◽  
In Situ Hybridisation ◽  
Cell Surface Receptor ◽  
Cellular Interactions ◽  
Spatial And Temporal Patterns ◽  
Cell Fate Decisions ◽  
Adult Rat ◽  
Surface Receptor ◽  
Notch Gene

Notch is a cell surface receptor that mediates a wide variety of cellular interactions that specify cell fate during Drosophila development. Recently, homologs of Drosophila Notch have been isolated from Xenopus, human and rat, and the expression patterns of these vertebrate proteins suggest that they may be functionally analogous to their Drosophila counterpart. We have now identified a second rat gene that exhibits substantial nucleic and amino acid sequence identity to Drosophila Notch. This gene, designated Notch2, encodes a protein that contains all the structural motifs characteristic of a Notch protein. Thus, mammals differ from Drosophila in having more than one Notch gene. Northern and in situ hybridisation analyses in the developing and adult rat identify distinct spatial and temporal patterns of expression for Notch1 and Notch2, indicating that these genes are not redundant. These results suggest that the great diversity of cell-fate decisions regulated by Notch in Drosophila may be further expanded in vertebrates by the activation of distinct Notch proteins.

scholarly journals Expression of Notch 1, 2 and 3 is regulated by epithelial-mesenchymal interactions and retinoic acid in the developing mouse tooth and associated with determination of ameloblast cell fate.

1995 ◽  
Vol 130 (2) ◽  
pp. 407-418 ◽  
Author(s):  
T A Mitsiadis ◽  
M Lardelli ◽  
U Lendahl ◽  
I Thesleff
Keyword(s):  
Retinoic Acid ◽  
Epithelial Cells ◽  
Cell Fate ◽  
Transmembrane Protein ◽  
Biological Effects ◽  
Expression Patterns ◽  
Notch 1 ◽  
Cell Fate Decisions ◽  
Notch Gene ◽  
Dental Epithelium

Notch 1, Notch 2, and Notch 3 are three highly conserved mammalian homologues of the Drosophila Notch gene, which encodes a transmembrane protein important for various cell fate decisions during development. Little is yet known about regulation of mammalian Notch gene expression, and this issue has been addressed in the developing rodent tooth during normal morphogenesis and after experimental manipulation. Notch 1, 2, and 3 genes show distinct cell-type specific expression patterns. Most notably, Notch expression is absent in epithelial cells in close contact with mesenchyme, which may be important for acquisition of the ameloblast fate. This reveals a previously unknown prepatterning of dental epithelium at early stages, and suggests that mesenchyme negatively regulates Notch expression in epithelium. This hypothesis has been tested in homo- and heterotypic explant experiments in vitro. The data show that Notch expression is downregulated in dental epithelial cells juxtaposed to mesenchyme, indicating that dental epithelium needs a mesenchyme-derived signal in order to maintain the downregulation of Notch. Finally, Notch expression in dental mesenchyme is upregulated in a region surrounding beads soaked in retinoic acid (50-100 micrograms/ml) but not in fibroblast growth factor-2 (100-250 micrograms/ml). The response to retinoic acid was seen in explants of 11-12-d old mouse embryos but not in older embryos. These data suggest that Notch genes may be involved in mediating some of the biological effects of retinoic acid during normal development and after teratogenic exposure.

glp-1 can substitute for lin-12 in specifying cell fate decisions in Caenorhabditis elegans

Development ◽  
1993 ◽  
Vol 119 (4) ◽  
pp. 1019-1027 ◽  
Author(s):  
K. Fitzgerald ◽  
H.A. Wilkinson ◽  
I. Greenwald
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Effector Proteins ◽  
Regulatory Sequences ◽  
Animal Kingdom ◽  
Cell Fate Decisions ◽  
Notch Gene ◽  
Epidermal Growth ◽  
Differential Gene ◽  
Mutant Phenotypes

Members of the lin-12/Notch gene family encode receptors for intercellular signals and are found throughout the animal kingdom. In many animals, the presence of at least two lin-12/Notch genes raises the issue of the significance of this duplication and divergence. In Caenorhabditis elegans, two lin-12/Notch genes, lin-12 and glp-1, encode proteins that are 50% identical, with different numbers of epidermal growth factor-like motifs in their extracellular domains. Many of the cell fate decisions mediated by lin-12 and glp-1 are distinct. Here, we express glp-1 protein under the control of lin-12 regulatory sequences in animals lacking endogenous lin-12 activity and find that glp-1 can substitute for lin-12 in mediating cell fate decisions. These results imply that the lin-12 and glp-1 proteins are biochemically interchangeable, sharing common ligand and effector proteins, and that the discrete lin-12 and glp-1 mutant phenotypes result from differential gene expression. In addition, these results suggest that the duplicate lin-12/Notch genes found in vertebrates may also be biochemically interchangeable.

scholarly journals Extracellular interactions and ligand degradation shape the nodal morphogen gradient

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Yin Wang ◽  
Xi Wang ◽  
Thorsten Wohland ◽  
Karuna Sampath
Keyword(s):  
Correlation Spectroscopy ◽  
Cell Surface Receptor ◽  
Morphogen Gradient ◽  
Axis Formation ◽  
Cellular Interactions ◽  
Fluorescence Correlation ◽  
Selective Ligand ◽  
Surface Receptor ◽  
First Time

The correct distribution and activity of secreted signaling proteins called morphogens is required for many developmental processes. Nodal morphogens play critical roles in embryonic axis formation in many organisms. Models proposed to generate the Nodal gradient include diffusivity, ligand processing, and a temporal activation window. But how the Nodal morphogen gradient forms in vivo remains unclear. Here, we have measured in vivo for the first time, the binding affinity of Nodal ligands to their major cell surface receptor, Acvr2b, and to the Nodal inhibitor, Lefty, by fluorescence cross-correlation spectroscopy. We examined the diffusion coefficient of Nodal ligands and Lefty inhibitors in live zebrafish embryos by fluorescence correlation spectroscopy. We also investigated the contribution of ligand degradation to the Nodal gradient. We show that ligand clearance via degradation shapes the Nodal gradient and correlates with its signaling range. By computational simulations of gradient formation, we demonstrate that diffusivity, extra-cellular interactions, and selective ligand destruction collectively shape the Nodal morphogen gradient.

Protease Expression in Dedifferentiated Parosteal Osteosarcoma

1999 ◽  
Vol 123 (3) ◽  
pp. 213-221
Author(s):  
Carsten Haeckel ◽  
Alberto G. Ayala ◽  
Kathrin Radig ◽  
A. Kevin Raymond ◽  
Albert Roessner ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cathepsin B ◽  
Proteolytic Enzymes ◽  
Expression Patterns ◽  
Metastatic Potential ◽  
Cell Surface Receptor ◽  
Parosteal Osteosarcoma ◽  
Surface Receptor ◽  
Bone Trabeculae ◽  
Immunohistochemical Techniques

Abstract Background.—Parosteal osteosarcoma with dedifferentiation provides a useful model to study tumor progression from an indolent locally aggressive neoplasm to highly lethal metastasizing malignancy. Up-regulation of the proteolytic enzymes participating in stromal degradation is known to promote invasive growth and metastasis of several human and experimental tumors. Methods.—The expression patterns of urokinasase plasminogen activator (u-PA), its cell-surface receptor (u-PAR), and cathepsin B were analyzed by immunohistochemical techniques in 11 cases of parosteal osteosarcoma and in 4 cases of dedifferentiated parosteal osteosarcoma. Results.—Both enzymes and the receptor were coexpressed in most tumor cells of parosteal and dedifferentiated parosteal osteosarcoma. Their expression was strikingly enhanced in the dedifferentiated high-grade component of the tumors. Tumor cells involved in bone production (ie, those adjacent to tumor produced bone trabeculae) exhibited equally strong expression of u-PA, u-PAR, and cathepsin B, regardless of their histologic grade. Expression of u{-}PA, u-PAR, and cathepsin B was undetectable in the “normalized” cells embedded in the well-developed tumor bone trabeculae. Conclusion.—These data indicate that u-PA and its interacting molecules, such as u-PAR and cathepsin B, may have some contributory effects on the metastatic potential of tumor cells in dedifferentiated parosteal osteosarcoma.

scholarly journals Estrogen Signaling Drives Ciliogenesis in Human Endometrial Organoids

Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2282-2297 ◽  
Author(s):  
Sandra Haider ◽  
Magdalena Gamperl ◽  
Thomas R Burkard ◽  
Victoria Kunihs ◽  
Ulrich Kaindl ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Expression Patterns ◽  
Estrogen Signaling ◽  
Ciliated Cells ◽  
Cell Fate Decisions ◽  
Primary Driver ◽  
Endometrial Epithelium ◽  
Cyclic Changes

Abstract The human endometrium is the inner lining of the uterus consisting of stromal and epithelial (secretory and ciliated) cells. It undergoes a hormonally regulated monthly cycle of growth, differentiation, and desquamation. However, how these cyclic changes control the balance between secretory and ciliated cells remains unclear. Here, we established endometrial organoids to investigate the estrogen (E2)-driven control of cell fate decisions in human endometrial epithelium. We demonstrate that they preserve the structure, expression patterns, secretory properties, and E2 responsiveness of their tissue of origin. Next, we show that the induction of ciliated cells is orchestrated by the coordinated action of E2 and NOTCH signaling. Although E2 is the primary driver, inhibition of NOTCH signaling provides a permissive environment. However, inhibition of NOTCH alone is not sufficient to trigger ciliogenesis. Overall, we provide insights into endometrial biology and propose endometrial organoids as a robust and powerful model for studying ciliogenesis in vitro.

scholarly journals Maximal STAT5-Induced Proliferation and Self-Renewal at Intermediate STAT5 Activity Levels

2008 ◽  
Vol 28 (21) ◽  
pp. 6668-6680 ◽  
Author(s):  
Albertus T. J. Wierenga ◽  
Edo Vellenga ◽  
Jan Jacob Schuringa
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Target Genes ◽  
Expression Patterns ◽  
Activity Levels ◽  
Dependent Manner ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Cell Fate Decisions

ABSTRACT The level of transcription factor activity critically regulates cell fate decisions, such as hematopoietic stem cell (HSC) self-renewal and differentiation. We introduced STAT5A transcriptional activity into human HSCs/progenitor cells in a dose-dependent manner by overexpression of a tamoxifen-inducible STAT5A(1*6)-estrogen receptor fusion protein. Induction of STAT5A activity in CD34+ cells resulted in impaired myelopoiesis and induction of erythropoiesis, which was most pronounced at the highest STAT5A transactivation levels. In contrast, intermediate STAT5A activity levels resulted in the most pronounced proliferative advantage of CD34+ cells. This coincided with increased cobblestone area-forming cell and long-term-culture-initiating cell frequencies, which were predominantly elevated at intermediate STAT5A activity levels but not at high STAT5A levels. Self-renewal of progenitors was addressed by serial replating of CFU, and only progenitors containing intermediate STAT5A activity levels contained self-renewal capacity. By extensive gene expression profiling we could identify gene expression patterns of STAT5 target genes that predominantly associated with a self-renewal and long-term expansion phenotype versus those that identified a predominant differentiation phenotype.

Differential expression of Notch component and effector genes during ovarian follicle and corpus luteum development during the oestrous cycle

2015 ◽  
Vol 27 (7) ◽  
pp. 1038 ◽  
Author(s):  
D. Murta ◽  
M. Batista ◽  
E. Silva ◽  
A. Trindade ◽  
L. Mateus ◽  
...  
Keyword(s):  
Corpus Luteum ◽  
Cell Fate ◽  
Ovarian Follicle ◽  
Expression Patterns ◽  
Cell Signalling ◽  
Cell Communication ◽  
Oestrous Cycle ◽  
Specific Expression ◽  
Cell Fate Decisions ◽  
Effector Genes

Ovarian dynamics throughout the female oestrous cycle (EC) are characterised by cyclical follicle and corpus luteum (CL) development. These events are tightly regulated, involving extensive cell-to-cell communication. Notch is an evolutionarily well conserved cell-signalling pathway implicated in cell-fate decisions in several tissues. Here, we evaluated the extra-vascular expression patterns of Notch component and effector genes during follicle and CL development throughout the EC. Five mature CD1 female mice were killed at each EC stage. Blood samples were collected for progesterone measurement, ovaries were processed for immunohistochemistry and expression patterns of Notch components (Notch1, 2 and 3, Jagged1 and Delta-like1 and 4) and effectors (Hes1, Hes2 and Hes5) were characterised. Nuclear detection of Notch effectors indicates that Notch signalling is active in the ovary. Notch components and effectors are differentially expressed during follicle and CL development throughout the EC. The spatial and temporal specific expression patterns are associated with follicle growth, selection and ovulation or atresia and CL development and regression.

Notch signaling in pathogenesis of diseases

2014 ◽  
Vol 2 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Christense ME ◽  
Carolan BS
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Gene Polymorphisms ◽  
Fixed Effects ◽  
Vascular System ◽  
Meta Analysis ◽  
Tumor Formation ◽  
Cell Fate Decisions ◽  
Pubmed Database ◽  
Notch Gene

The Notch signaling pathway functions on cell fate decisions in a variety of different organizations in multicellular organisms, such as the hematopoietic system, nervous system, vascular system, skin and pancreas. In the majority of cases, Notch signaling blocks cell differentiation towards a primary process, and instead, direct them to a second differentiation. Altering the differentiation program or forcing it to remain in the undifferentiated state, there are several human diseases linked to defects in genes involved in Notch signaling, aberrant Notch signaling has been observed in a number of human cancers, suggesting a possible role of Notch signaling in tumor formation. Further, Recent study demonstrated an essential role for Notch1 in the corneal epithelial barrier recovery after wounding. We systematically searched the electronic PubMed database for research articles about Notch gene polymorphisms and diseases up to October 2013. Revman 5.0 software was adopted to conduct the meta-analysis. Crude odds ratio (ORs) and 95% confidence intervals (95% CIs) were calculated by either fixed-effects model or random-effects model. The present meta-analysis suggests that Notch gene polymorphisms are associated with the susceptibility of many diseases especially cancer.

Notch signaling in pathogenesis of diseases

2014 ◽  
Vol 2 (1) ◽  
pp. 1-4
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Gene Polymorphisms ◽  
Fixed Effects ◽  
Vascular System ◽  
Meta Analysis ◽  
Tumor Formation ◽  
Cell Fate Decisions ◽  
Pubmed Database ◽  
Notch Gene

The Notch signaling pathway functions on cell fate decisions in a variety of different organizations in multicellular organisms, such as the hematopoietic system, nervous system, vascular system, skin and pancreas. In the majority of cases, Notch signaling blocks cell differentiation towards a primary process, and instead, direct them to a second differentiation. Altering the differentiation program or forcing it to remain in the undifferentiated state, there are several human diseases linked to defects in genes involved in Notch signaling, aberrant Notch signaling has been observed in a number of human cancers, suggesting a possible role of Notch signaling in tumor formation. Further, Recent study demonstrated an essential role for Notch1 in the corneal epithelial barrier recovery after wounding. We systematically searched the electronic PubMed database for research articles about Notch gene polymorphisms and diseases up to October 2013. Revman 5.0 software was adopted to conduct the meta-analysis. Crude odds ratio (ORs) and 95% confidence intervals (95% CIs) were calculated by either fixed-effects model or random-effects model. The present meta-analysis suggests that Notch gene polymorphisms are associated with the susceptibility of many diseases especially cancer.

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